Interstitial cystitis (IC) is a sterile bladder condition of unknown etiology characterized by increased urinary urgency and frequency as well as suprapubic pain. Two important features of the disorder that must be explained are that: 1) IC affects predominantly females, and 2) IC patients exhibit enhanced sensitivity to bladder distention. In addition, clinical observation suggests that symptoms of IC are exacerbated perimenstrually. The research proposed in this exploratory/developmental (R21) grant application is based on the overriding hypothesis that these clinical features can, at least in part, be explained by a generalized alteration in central nervous system nociceptive processing in IC, which is influenced by the hormonal fluctuations that accompany the female menstrual cycle. Based on this hypothesis two predictions regarding IC will be investigated: first, that IC is associated with a generalized increase in pain sensitivity, which includes enhanced responses to somatic as well as visceral stimuli; and second, that both clinical symptoms and responses to experimentally-evoked pain will be influenced by the menstrual cycle in IC patients. In order to examine these predictions, the responses of IC patients and healthy, female controls to three clinically relevant laboratory pain induction procedures will be evaluated: a) temporal summation of thermal pain, b) ischemic arm pain, and c) visceral pain produced by fluid distention of the urinary bladder. In addition, clinical symptoms as well as responses to the same three experimental pain procedures will be assessed across the menstrual cycle in both IC patients and controls. It is anticipated that: 1) IC patients will demonstrate greater sensitivity to both somatic and visceral pain stimuli relative to controls; 2) clinical symptoms will be greater among IC patients during the luteal versus the follicular phase of the menstrual cycle, while menstrual cycle effects on clinical symptoms among controls will be minimal; and 3) experimental pain sensitivity for both groups will be greater during the luteal versus the follicular phase; however, the menstrual cycle effect will be greater for IC patients than controls. The results of this research will provide important and novel information regarding pain sensitivity and menstrual cycle effects in IC and will establish a foundation of knowledge to support more extensive investigations of hormonal influences on nociceptive processing in interstitial cystitis.